MPTP: advances from an evergreen neurotoxin

Since its discovery in 1976, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models in rodents and nonhuman primates have continuously renewed to keep up with progresses of Parkinson’s disease (PD) research. MPTP is able to reproduce almost all the clinical and neuropathological features of PD when administered to monkeys. In contrast, up to date no rodent model has been able to reproduce all PD features in one. Nevertheless, MPTP is a very versatile neurotoxin that can reproduce different aspects of PD pathology, depending upon the dose and regimen of administration. At the present time, a number of different MPTP models have been developed, allowing researchers to investigate either the classical PD neuropathology and neuroprotective mechanisms or known pathological processes underlining more recently discovered aspects of the disease, such as nonmotor symptoms. In this chapter primate and rodent MPTP models are reviewed, focusing mainly on the contribution that different MPTP protocols can offer to reproduce the multifaceted aspects of the disease

Dementia associated with disorders of the basal ganglia

Dementia is now the leading cause of death in the United Kingdom, accounting for over 12% of all deaths and is the fifth most common cause of death world-wide. As treatments for heart disease and cancers improve and the population ages, the number of sufferers will only increase, with the chance of developing dementia doubling every 5 years after the age of 65. Finding an effective treatment is ever more critical to avert this pandemic health (and economic) crisis. To date, most dementia-related research has focused on cortex and hippocampus, however, with dementia becoming more fully recognized as aspects of diseases historically categorized as motor disorders (e.g. Parkinson’s and Huntington’s diseases), the role of the basal ganglia in dementia is coming to the fore. Conversely, it is highly likely that neuronal pathways in these structures traditionally considered as spared in Alzheimer’s disease are also affected, particularly in later stages of the disease. In this review we examine some of the limited evidence linking the basal ganglia to dementia